The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18–25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes’ expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Thermo-physical properties of as deposited and aged thermal barrier coatings (TBC) for gas turbines: State-of-the art and advanced TBCs

In the perspective of fuelling the future generations of gas turbines by hydrogen rich syngas, the evaluation of the effect of a higher water vapour content into the flue gases on the TBC used, or potentially usable, is a need. For this purpose YPSZ APS TBC with two different microstructures have been exposed for 500?h at different temperatures in the range 1000?°C–1250?°C either in air and air +20% vol. H₂O. The comparison between the different testing conditions has been performed in terms of sintering kinetics and phase stability, as evaluated by thermal diffusivity measurements and Synchrotron X-Rays diffraction, respectively. Furthermore the characterisation of thermal properties of two innovative TBCs (GZO-YPSZ and YAG) potentially able to withstand the CMAS attack and erosive environments, respectively, has been carried out.No clear evidence of a different behaviour of TBC has been observed, at least in the considered aging time and temperature range.     

Application of the novel Droplet digital PCR technology for identification of meat species

The authenticity and traceability of meat products are issues of primary importance to ensure food safety. Unfortunately, food adulteration (e.g. the addition of inexpensive cuts to minced meat products) and mislabelling (e.g. the inclusion of meat from species other than those declared) happens frequently worldwide. The aim of this study was to apply a droplet digital PCR assay for the detection and quantification (copies μL⁻¹) of the beef, pork, horse, sheep, chicken and turkey in meat products. The analysis conducted on commercial meat showed the presence of traces of DNA from other animal species than those declared. We show that the method is highly sensitive, specific and accurate (accuracy = 100%). This method could be adopted by competent food safety authorities to verify compliance with the labelling of meat products and to ensure quality and safety throughout the meat supply chain, from primary production to consumption.     

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

Background  

Excess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individual's Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m². The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.     

Development of New Sulphonyl Resin from Modification of Commercial Resin

Summary This article deals with the handy synthesis of sulfonyl resins, which were produced by the treatment of a commercial sulfonic resin (Lewatit VPOC1812^® based at divinylbenzene (DVB) and styrene (STY). The preliminary chemical modification was based on the reaction of the Lewatit VPOC1812^® with thionyl chloride aiming to produce the sulfonyl chloride groups. The best conditions to obtain the sulfonyl chloride groups were: SOCl₂/SO₃H (molar ratio) =13 at 79 °C during 72 h. The resin chlorinated was afterward treated with urea, thiourea or guanidine. The functionalized resins with urea, thiourea or guanidine were produced with 56, 68 and 93% yield, respectively. The commercial and modified resins were characterized by apparent density, swelling degree, elemental analysis (CHNS), FTIR, optical microscopy (OM) and scanning electron microscopy (SEM).     

High-electric-field effects and degradation of AlGaAs/GaAs power HFETs: a numerical study

This work presents a numerical study of high-field degradation and reliability issues of AlGaAs/GaAs power HFETs. A commercial two-dimensional drift–diffusion tool is used to investigate electric-field distributions, the effects of electron capture at the device surface under hot-carrier conditions, and the impact of drain recess scaling on such effects. Wherever experimental data are available for direct comparison, a good match is observed with our simulations. The main results of this study are (1) a validation of the hypothesis that attributes the main high-field degradation effects to electron capture over the gate–drain access region, and (2) design indications pointing out to the possibility of a reverse correlation between the gate–drain breakdown voltage and the device hot-carrier reliability.     

XV. Yeast sequencing reports. Isolation and DNA sequence of the STE13 gene encoding dipeptidyl aminopeptidase

We have isolated a mutant which exhibits partial constitutivity for a -specific gene expression in α cells. The wild-type gene was cloned and demonstrated to be allelic to the STE13 gene, which encodes the dipeptidyl aminopeptidase involved in processing of the α-factor prepropheromone. Thus, the mating defect of the ste13 mutations in α cells may result both from the production of incompletely processed α-factor and from the increased expression of a -specific genes. The STE13 open reading frame of 931 amino acids contains a putative membrane-spanning segment near its amino terminus and is 31% identical to a second yeast dipeptidyl aminopeptidase (DAP2). A null mutant of STE13 has been constructed: it is viable and sporulation-proficient. The sequence has been deposited in the GenBank data library under Accession Number L21944.     

Development of spontaneous classificatory behavior in chimpanzees (Pan troglodytes).

Investigated the development of spontaneous classificatory behavior in 5 chimpanzees (Pan troglodytes) tested at different ages and analyzed Ss' spontaneous constructive interactions with sets of logically structured objects. The results show that chimpanzees possess a natural capacity to react to similarities and differences among test stimuli and construct classes. The general progression of their classificatory development is very similar to that reported for human infants from 6 to 24 mo. In both species, classification progresses from constructing single classes by different properties of objects to constructing single classes by similar or identical properties of objects. In addition, like humans, older chimpanzees spontaneously coordinate relations of similarities between sets and construct 2 class-consistent groupings. Chimpanzees' results are compared with those from a similar study with capuchins and macaques. (PsycINFO Database Record (c) 2010 APA, all rights reserved)